In order to effectively correct genetic disorders in humans, safe and efficient gene delivery systems must be[unreadable] developed, produced in large quantities, purified from contaminants, free of replication competent virus[unreadable] (RCV) and concentrated to high titers. The engineering of effective gene transfer vectors has been a crucial[unreadable] factor for the efficient delivery and expression of therapeutic gene products in vivo. Viruses have been[unreadable] adapted for use as gene transfer vectors taking advantage of natural viral mechanisms designed to[unreadable] efficiently and effectively deliver DMA to the host cell nucleus. Among these, herpes simplex virus type 1[unreadable] (HSV-1) represents an excellent candidate vector for delivery to the peripheral (PNS) and central nervous[unreadable] systems (CMS) based on the natural biology of the virus that includes the establishment of a life-long latent[unreadable] state in neurons in which the viral genome persists as an episomal molecule. Considerable effort in the[unreadable] development of HSV-1 vectors has resulted in the engineering of totally replication defective vectors that are[unreadable] non-toxic for neurons and are capable of long-term transgene expression in neurons of the PNS. As well,[unreadable] efforts in process development have resulted in scaleable systems capable of manufacturing these vectors[unreadable] for pre-clinical efficacy and safety testing. The primary goal of the Pre-Clinical Vector Core will be to provide[unreadable] large quantities of concentrated and purified HSV-1 vectors expressing single or multiple therapeutic genes[unreadable] to each of the projects for the proposed experiments. The Pre-Clinical Vector Core will work with the[unreadable] projects to provide optimal vector quantity and purity. The proposed design of the Pre-Clinical Vector Core[unreadable] will be to provide the support necessary to successfully exploit the available technology.[unreadable] The specific aims of the Pre-Clinical Vector Core are: (1) to provide each investigator with the appropriate[unreadable] purified HSV-1 vector already in-hand expressing the required therapeutic or marker gene to successfully[unreadable] complete the proposed pre-clinical experiments; and (2) to provide technical assistance, reagents, and[unreadable] protocols to each of the projects including the development of new or modified protocols for the production[unreadable] and purification of HSV vectors for pre-clinical experiments. Should success in these projects lead to the[unreadable] initiation of Phase-l human clinical trials, the Pre-Clinical Vector Core is set up to transition the production of[unreadable] these vectors to the Human Gene Therapy Applications Laboratory (HGTAL) as part of the University of[unreadable] Pittsburgh Molecular Medicine Institute (MMI).